Inclusion Criteria:

- Ability to understand and the willingness to sign a written informed consent document

- Histologically or cytologically confirmed stage IV squamous cell carcinoma of the
oral cavity or oropharynx staged according to AJCC guidelines

- T4 staged tumor with a tumor volume greater than or equal to 30 cc

- Nodal staging of N0 through 2a

- No evidence of distant metastatic disease, as determined by a negative PET scan or
other clinically appropriate means

- Age ≥ 18

- Clinically eligible for both intra-arterial and intravenous administration of
cisplatin

- Women of childbearing potential must have a negative pregnancy test.

- Agree to use adequate contraception prior to study entry and for the duration of
study participation and for 3 months after study treatment ended

- Biopsiable via a transoral approach

- Life expectancy of at least 5 years

- ECOG performance status ≤ 2

- Measurable disease as defined by RECIST criteria

- Absolute neutrophil count ≥ 1,000/mm3

- Hemoglobin ≥ 8.0 g/dl

- Platelet count ≥ 100,000/mm3

- Leukocytes≥3500/mcL

- Total Bilirubin ≤ ULN of institution performing testing

- Creatinine within normal institutional limits

Exclusion Criteria:

- Radiologic evidence of bone destruction

- Tumor with involvement of cartilage or bone

- Requires bilateral IA infusion with radiologist determination that tumor extends
across the midline in excess of 30% of the tumor volume

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to agents and pre-medications used in the study, including drugs
formulated with polysorbate 80

- Allergy to cardiac catheterization contrast agents, in which antihistamines are not
sufficient to suppress a reaction or severe enough to pose a significant danger to
the subject

- History of stroke, CABG, or significant blockage of carotid arteries or coronary
arteries or current blockage of coronary or carotid arteries equal to or in excess of
50% blockage; Interventional radiology must agree that the patient is a good
candidate for catheterization.

- Intolerance to IV, IA, or radiation therapy treatment for any reason as determined by
the procedural physician

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnancy

- Breast feeding women

- Prior or concurrent non-head and neck malignancies, excluding adequately treated
basal or squamous cell cancer of the skin, in situ cervical cancer, stage I or II
cancer from which the subject has been in complete remission for at least 12 months,
any cancer from which the subject has been cancer free for 5 years

- Tumor site which cannot provide a biopsy in the clinic via punch or core needle
biopsy performed

- Second primary head and neck tumor (concurrent or previous head and neck tumor unless
it was a basal or squamous cell skin cancer)

- Unknown primary tumor site

- Prior surgery, chemotherapy, biologic or radiotherapy for a head or neck malignancy
(excluding minor surgical procedures for skin cancer)

- History of surgery (non-oncologic) in the field of the tumor or treatment bed.

- Participation in an investigational treatment or intervention study within 90 days of
screening visit

- calculated creatinine clearance less than 60 mL/min/1.73 m2